The purpose of this project is to understand cytokine regulation in animals infected with Histoplasma Capsulatum. Histoplasmosis is a disease found in certain geographic regions of this country. In a normal host the disease will often be controlled without significant end organ damage. However, patients infected with HIV have a difficulty in eradicating the disease. Therefore it was of interest to study mechanisms which might alter the immune response to this organism with the goal of protecting the animal. Previous work had demonstrated that the organism resides in mononuclear phagocytic cells. Moreover, it was shown that the presence of IFNg enables the macrophage to kill the organism. Recently, a new cytokine, IL- 12 has been shown to be a potent inducer of IFNg from both T cells and NK cells. Thus we set out to investigate the role that IL-12 had in the course of the disease and how it affected cytokine production especially IFNg. We injected mice with a human isolate of Histoplasma Capsulatum, and then injected them with various cytokines at the onset of infection and followed them for mortality . We found that mice infected with 6x105 organisms died two weeks following infection. If mice were treated with an antibody against IFNg at the time of infection to neutralize endogenous IFNg, then death occurred in 7-10 days. Mice treated with IL-12 at the time of infection were still alive at two months. This data indicates that IFNg is critical for host protection and exogenous IL-12 can enhance survival. Further studies will be done to examine the cytokines made by the animal and determine whether mice receiving IL-12 had diminished number of organisms.